There are 4 specific aims all connected with the problems of glaucoma which damages the optic nerve through elevated intraocular pressure. Two important groups of drugs in this disease are carbonic anhydrase inhibitors and cholinergic stimulants such as pilocarpine. The mechanism by which moderately elevated pressure damages the nerve is not clear. Nor is it understood how carbonic anhydrase inhibitors can act with so relatively little side actions and how pilocarpine can be effective for long periods of time despite subsensitivity of the ciliary muscle. The planned research deals with these questions. Axoplasmic transport in the optic nerve of rats and other small rodents in vitro, at different intraocular pressures set artifically, will test the pressure sensitivity of optic nerve fibers as such. Chronic actions of carbonic anhydrase inhibitors will be studied with enzyme histochemistry, immunofluorescence and immunologic titration of isoenzymes in many organs of treated rats. We hope to find an adaptive response of one of the isoenzymes. Cholinergic subsensitivity of the rabbit iris muscle in vitro will be studied pharmacologically to clarify the site of the subsensitivity - membrane receptor loss is probably only part of the story. Drugs that reduce intraocular pressure by inhibiting fluid formation are becoming more important. We try to develop a technique for measuring aqueous fluid formation in the alert monkey because anaesthesia depresses the formation of the fluid.